慢性脊髓損傷病患膀膀上皮E -鈣粘蛋白(E-cadherin)以及緊密連接蛋白(Zonula Occludens-1)缺損經過反覆肉毒桿菌素膀胱逼尿肌注射具有療效
陳聖復1、張嘉慧1、郭漢崇1
1佛教花蓮慈濟綜合醫院泌尿部
Deficits of Urothelial E-cadherin and Zonula Occludens-1 in Chronic Spinal Cord Injured Bladders Improved after Repeated Detrusor OnabotulinumtoxinA Injections
Sheng-Fu Chen1, Chia-Hwei Chang1, Hann-Chorng Kuo1
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University1
Purpose: Chornic spinal cord injury (SCI) induces bladder urothelium dysfunction. This study investigated the therapeutic effects on urothelial dysfunction after repeated detrusor injections of onabotulinumtoxinA in patients with SCI and neurogenic detrusor overactivity (NDO).
Materials and Methods: A total of 20 patients with chronic suprasacral SCI and refractory NDO were enrolled. The patients received 300U onabotulinumtoxinA detrusor injection every 6 months for four times. The urothelium was assessed by cystoscopic biopsy at baseline and 6 months after each onabotulinumtoxinA treatment. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), and tryptase for mast cell activity were performed. Urothelial apoptosis was also evaluated. The differences in urothelial dysfunction were compared between baseline and every 6 months after treatment. Bladder biopsies from 10 patients undergoing anti-incontinence surgery served as controls.
Results: Repeated 300U onabotulinumtoxinA injections into the detrusor significantly and consistently increased bladder capacity and decreased detrusor pressure at 6 months after each onabotulinumtoxinA treatment compared with baseline. Significantly lower E-cadherin and ZO-1 expressions, and increased apoptotic cell counts were noted in SCI bladders compared with controls (all P<0.05). After repeated onabotulinumtoxinA injections, significantly greater distributions of E-cadherin (p=0.042) and ZO-1 (p=0.003) expressions were found at 6 months after 3rd onabotulinumtoxinA injection compared with baseline. Besides, after 3rd onabotulinumtoxinA treatment, no significant difference of E-cadherin and ZO-1 were noted compared to the control.
Conclusions: Urothelial dysfunction parameters such as adhesive and tight junction protein concentrations in SCI bladders recovered after repeated 3 times of onabotulinumtoxinA treatment. The therapeutic effects also sustained after repeated onabotulinumtoxinA treatment. However, neurogenic inflammation and urothelial cell apoptosis after SCI could not adequately improve after repeated onabotulinumtoxinA injection.